The proposed research involves the study of inhibitors, both synthetic and natural, of the tRNA methyltransferases. We are studying the effect of analogs of S-adenosylhomocysteine and nucleoside analogs as inhibitors of methylation both in vitro and in vivo. We are also studying the action of two carcinogens, ethionine and 5-azacytidine, on methylation in vitro and in vivo. Other studies include the effects of tRNA metabolites, methylated purines, on growth properties of normal cells in culture.